SUMMARY The intransigence of malaria in Malawi frustrates policy makers, implementers (e.g., the National Malaria Control Programme - NMcp) and the clinicians and epidemiologists grappling with malaria treatment, prevention and control, at the individual and community levels. Exciting new tools ? a bed net treated with an enzyme (piperonyl butoxide, PBO) that reduces insecticide resistance in mosquito vectors, and a malaria vaccine (RTS,s/SA01, abbreviated RTS,S) ? will both be deployed by NMcp, WHO and others, through pilot studies in selected districts in Malawi. Our International Centers of Excellence in Malaria Research (ICEMR) team is well established in two of the selected districts, Machinga and Balaka. Households in both districts will be randomized to receive the malaria vaccine, or not. The new ITNs with PBO will be distributed to some districts, including Machinga. The populations in other districts, including Balaka, will receive conventional (pyrethroid only) nets. The effectiveness of interventions is critically dependent on their acceptability to individuals, households, and communities. In conjunction with these pilot studies of RTS,S and PBO nets, we will use a mix of qualitative and quantitative methods to collect socio-behavioral data on: ? A new forum for providing information on malaria prevention interventions (Mother Care Groups) ? A new platform for education and interventions, namely schools ? The new PBO net acceptance and use, as well as another net type that may discourage misuse. The combination of these two pilot studies, coupled with our on-the-ground expertise in entomological assessments, socio-behavioral research, epidemiological data capture and management, collection, storage and transfer of biological sample, their molecular analysis, and biostatistical examination creates a highly unusual opportunity to identify the ?real world? effectiveness of both conventional and new approaches to malaria prevention and control, and to capture, at community level, the determinants of their acceptability. The Malawi ICEMR is ready to go. We have been involved in the design of the pilot studies, we have roots in the relevant communities, and this opportunity represents an opportunity to expand our study of the stubborn, refractory nature of Plasmodium infection/transmission, and malaria disease, in Malawi.